A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma

Abstract

Purpose Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin Lymphoma (HL). The goal of this trial was to learn the anti-tumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients and Methods Patients were eligible if they had measurable disease, a platelet count ≥75,000 and an absolute neutrophil count ≥1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after 2 and 6 cycles and then every 3 cycles until progression. Patients could remain on drug until progression or toxicity. Results Nineteen patients were enrolled. Median age was 37 years (range, 27-68). Patients had received a median of 6 prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with 8 patients achieving a PR and 1 patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of 7 cycles of therapy. Of the 19 patients, 1 remains on therapy at 36 months; the others went off-study due to progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a grade three or higher pulmonary toxicity. Conclusions Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.

Hodgkin lymphoma: MOPP chemotherapy to PD‐1 blockade and beyond

“…High response rates have been seen with the use of everolimus, an oral antineoplastic agent targeting the mTOR complex 1 (mTORC1) molecule within this pathway [30]. A clinical trial of everolimus administered at the dose of 10 mg daily by mouth was performed, and in this trial of 19 patients with relapsed and refractory Hodgkin lymphoma, 84% of the patients had previously received an autologous stem cell transplant.…”

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

“…A PI3K/m-TOR gátlók közül az everolimust próbálták ki HL-es betegekben. Azonban az ezekkel a készítmé-nyekkel elért eredmények szerények [45,46,47].…”

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

“…Inhibition of Akt in HL cell lines leads to apoptosis, suggesting that the PI3K-AktmTOR pathway has a role in growth and survival of RS cells. 27,40 Johnston et al 41 provided a proof-of-concept phase 2 trial enrolling 19 (84% had undergone prior auto-HCT) patients with relapsed HL showing an ORR of 47% and a median time-toprogression of 7.2 months (Table 1). Everolimus is also synergistic with other agents.…”